Steroid-Functionalized Titanocenes: Docking Studies with Estrogen Receptor Alpha

Abstract

Estrogen receptor alpha (ERα) is a transcription factor that is activated by hormones, with 17β-estradiol being its most active agonist endogenous ligand. ERα is also activated or inactivated by exogenous ligands. ER is overexpressed in hormone-dependent breast cancer, and one of the treatments for this type of cancer is the use of an ER antagonist to halt cell proliferation. We have previously reported four steroid-functionalized titanocenes: pregnenolone, dehydroepiandrosterone (DHEA), trans-androsterone, and androsterone. These steroids have hormonal activity as well as moderate antiproliferative activity, thus these steroids could act as vectors for the titanocene dichloride to target hormone-dependent cancers. Also, these steroids could increase the antiproliferative activity of the resulting titanocenes based on synergism. In order to elucidate which factors contribute to the enhanced antiproliferative activity of these steroid-functionalized titanocenes, we performed docking studies between ERα and the titanocenes and the steroids. The binding affinities and type of bonding interactions of the steroid-functionalized titanocenes with ERα are herein discussed.

Crystalline bis(η5-cyclopentadienyl)bis(benzoato/carboxylato)titanium(IV) precursor-directed route to functional titanium dioxide nanomaterials

“…However, Cp2TiCl2 did not advance in clinical trials owing to its low efficacy against the examined tumours and because of its inherent limitations such as poor water-solubility and instability, the latter due to extensive hydrolysis [13][14][15]. In spite of the unsatisfactory results of the phase II clinical trials, various researchers have continued investigations into titanium-based drugs, sparking interest in the synthesis of secondgeneration titanocene and titanium(IV) complexes with anti-cancer properties [16][17][18][19][20][21][22][23][24].…”

Ferrocene and titanocene steroid conjugates: Structures and activities – a brief review

“…Structures eight titanocene steroid conjugates (26)(27)(28)(29)(30)(31)(32)(33) have been synthesized and structures have been characterized. [8,10,[44][45][46] The anti-proliferative activity of (26)(27)(28)(29)(30)(31)(32)(33) was determined in colon cancer HT29 and breast cancer MCF-7 cell lines. Titanocenyl containing cholesterol rings with IC 50 values over 200 μM, with the exception of complex (30) and highly active titanocenyls containing sex steroids with IC 50 values below 50 μM on MCF-7 cell line were reported.…”

Mono- and di-anionic coordination modes of arylazosalicylates in their bis(η5-cyclopentadienyl)titanium(IV) complexes: Syntheses and crystal structures

“…Organometallic and coordination titanium(IV) compounds are of interest due to their reactivity and uses including as reagents for catalytic enantioselective processes [1], organic transformations [2], as initiators for polymerization reactions [3], polymerisation catalysts [4][5][6][7][8][9][10] to metal organic frameworks [11][12][13] and metallo-supramolecular chemistry [14][15][16][17][18][19]. Other applications include the use of alkoxides or aryloxides precursors for the generation of titaniumbased materials [20][21][22][23][24][25][26] and their uses as photo-sensitisers and photo-catalysts [27,28], titaniumbased drugs [29][30][31][32][33][34][35][36][37][38][39] and cell imaging [40][41]. In recent years, substituted titanium-oxo-clusters, such as those substituted by acetylacetonate, carboxylates and catecholate derivatives, have attracted a great deal of attention, owing to their hydrolytic stability and versatile coordination modes [42][43][44]…”